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Background There have been no recent population-based studies on all-cause adult neurological morbidity in sub‐Saharan Africa. We have developed a screening survey to improve the feasibility in performing these studies. Methods Our screening instrument contains both history questions and examination items. We pilot tested this instrument in the Hai District, Tanzania, and Butajira, Ethiopia using trained individuals from the local communities. To measure sensitivity, we applied the instrument blindly to 25 previously-identified subjects with Parkinson's disease, stroke or epilepsy. To measure specificity, we examined 42 randomly selected previously screened subjects. We also compared the validity of the entire instrument to the history-only section. Results There were 669 adult subjects screened in both communities (150 screen-positives, and 519 screen-negatives). The sensitivity of the instrument was 100% (95% CI 84.2–100%) and the specificity was 82.4% (95% CI 66.1–92.0%). However, when restricting the instrument to the history-only section, the sensitivity remained unchanged, but the specificity became 91.2% (95% CI 76.3–97.7%; p = 0.48). Conclusions We have created a valid tool to screen adults for neurologic morbidity in resource-poor communities. The use of the history-only section of the tool is adequate as a screen and will improve feasibility.

Background Compulsive behaviors provoked by dopamine agonists often go undetected in clinical series, especially if not specifically inquired about. Aim To determine the frequency of compulsive behaviors in a Parkinson’s disease (PD) clinic where agonist-treated patients were routinely asked about such aberrant behaviors. Methods We utilized the Mayo Health Science Research database to ascertain all PD patients taking a dopamine agonist over a two year period (2007–2009). All were seen by a Mayo-Rochester Movement Disorders Staff specialist who routinely inquired about behavior compulsions. Results Of 321 PD patients taking an agonist, 69 (22%) experienced compulsive behaviors, and 50/321 (16%) were pathologic. However, when the analysis was restricted to patients taking agonist doses that were at least minimally therapeutic, pathological behaviors were documented in 24%. The subtypes were: gambling (25; 36%), hypersexuality (24; 35%), compulsive spending/shopping (18; 26%), binge eating (12; 17%), compulsive hobbying (8; 12%) and compulsive computer use (6; 9%). The vast majority of affected cases (94%) were concurrently taking carbidopa/levodopa. Among those with adequate followup, behaviors completely or partly resolved when the dopamine agonist dose was reduced or ceased. Conclusions Dopamine agonist treatment of PD carries a substantial risk of pathological behaviors. These occurred in 16% of agonist-treated patients; however, when assessing patients whose dose was at least minimally in the therapeutic range, the frequency jumped to 24%. Pathological gambling and hypersexuality were most common. Carbidopa/levodopa therapy taken concurrently with a dopamine agonist appeared to be an important risk factor.

Approximately 26,000,000 people live in sub-Saharan African (SSA) nations where there are no neurologists. A total of 270,000,000 live in nations where there are fewer than 5 neurologists per country.1 There are neurologic societies in fewer than 50% of SSA countries.2 The WHO recommends a ratio of 1 neurologist:100,000 people. In those SSA nations where there are neurologists, the ratio is up to 175 times that recommended by the WHO.1 The authors thank Dr. Johan Aarli, previous President of the World Federation of Neurology, Dr. Jacques de Reuck, previous President of the EFNS, and Dr. Jean-Michel Vallat, previous Chair of the sub-Saharan African Task Force, for initiating these teaching courses; and Eveline Sipido for administration of the courses.

Participation rates in epidemiologic studies in African communities are historically high. We recently performed a pilot prevalence study for neurologic morbidity in Mungushi, Tanzania, where the participation rate was 645/657 subjects (98.2%).1 We questioned whether this high rate was due to a sincere motivation to participate or a fear of refusal of participation. As Western investigators are increasingly performing neuroepidemiologic work in Africa, it is imperative to distinguish between the 2 explanations. Investigators need to tailor the consent process to the local community's needs, and be sensitive to the motivation of the participants whose culture may differ from their own.

We studied the association of three personality traits related to neuroticism with the subsequent risk of Parkinson's disease (PD) using a historical cohort study. We included 7,216 subjects who resided within the 120-mile radius centered in Rochester, MN, at the time they completed the Minnesota Multiphasic Personality Inventory (MMPI) for research at the Mayo Clinic from 1962 to 1965. We considered three MMPI personality scales (pessimistic, anxious, and depressive traits). A total of 6,822 subjects (94.5%) were followed over four decades either actively or passively. During follow-up, 227 subjects developed parkinsonism (156 developed PD). An anxious personality was associated with an increased risk of PD [hazard ratio (HR), 1.63; 95% confidence interval (CI), 1.16-2.27]. A pessimistic personality trait was also associated with an increased risk of PD but only in men (HR = 1.92; 95% CI = 1.20-3.07). By contrast, a depressive trait was not associated with increased risk. Analyses combining scores from the three personality scales into a composite neuroticism score showed an association of neuroticism with PD (HR = 1.54; 95% CI = 1.10-2.16). The association with neuroticism remained significant even when the MMPI was administered early in life (ages 20-39 years). By contrast, none of the three personality traits was associated with the risk of non-PD types of parkinsonism grouped together. Our long-term historical cohort study suggests that an anxious personality trait may predict an increased risk of PD developing many years later.

BackgroundGlycine receptor alpha-1 subunit (GlyRα1)-immunoglobulin G (IgG) is diagnostic of stiff-person syndrome (SPS) spectrum but has been reported detectable in other neurologic diseases for which significance is less certain.MethodsTo assess GlyRα1-IgGs as biomarkers of SPS spectrum among patients and controls, specimens were tested using cell-based assays (binding [4°C] and modulating [antigen endocytosing, 37°C]). Medical records of seropositive patients were reviewed.ResultsGlyRα1-IgG (binding antibody) was detected in 21 of 247 patients with suspected SPS spectrum (8.5%) and in 8 of 190 healthy subject sera (4%) but not CSF. Among 21 seropositive patients, 20 had confirmed SPS spectrum clinically, but 1 was later determined to have a functional neurologic disorder. Sera from 9 patients with SPS spectrum , but not 7 controls, nor the functional patient, caused GlyRα1 modulation (100% specificity). SPS spectrum phenotypes included progressive encephalomyelitis with rigidity and myoclonus (PERM) (8), classic SPS (5), stiff limb (5), stiff trunk (1), and isolated exaggerated startle (hyperekplexia, 1). Neuropsychiatric symptoms present in 12 patients (60%) were anxiety (11), depression (6), and delirium (3). Anxiety was particularly severe in 3 patients with PERM. Objective improvements in SPS neurologic symptoms were recorded in 16 of 18 patients who received first-line immunotherapy (89%, 9/10 treated with corticosteroids, 8/10 treated with IVIg, 3/4 treated with plasma exchange, and 1 treated with rituximab). Treatment-sparing maintenance strategies were successful in 4 of 7 patients (rituximab [2/3], azathioprine [1/1], and mycophenolate [1/3]).ConclusionsGlyRα1-modulating antibody improves diagnostic specificity for immunologically treatable SPS spectrum disorders.Classification of evidenceThis study provides Class IV evidence that GlyRα1-modulating antibody accurately identifies patients with treatable SPS spectrum disorders.

Objective: Parkinson disease (PD) may affect the autonomic nervous system and may cause constipation; however, few studies have explored constipation preceding the motor onset of PD. We investigated constipation preceding PD using a case-control study design in a population-based sample. Methods: Using the medical records-linkage system of the Rochester Epidemiology Project, we identified 196 subjects who developed PD in Olmsted County, MN, from 1976 through 1995. Each incident case was matched by age (±1 year) and sex to a general population control. We reviewed the complete medical records of cases and controls in the medical records-linkage system to ascertain the occurrence of constipation preceding the onset of PD (or index year). Results: Constipation preceding PD or the index year was more common in cases than in controls (odds ratio [OR] 2.48; 95% confidence interval [CI] 1.49 to 4.11; p = 0.0005). This association remained significant after adjusting for smoking and coffee consumption (ever vs never), and after excluding constipation possibly induced by drugs. In addition, the association remained significant in analyses restricted to constipation documented 20 or more years before the onset of motor symptoms of PD. Although the association was stronger in women than in men and in patients with PD with rest tremor compared with patients with PD without rest tremor, these differences were not significant. Conclusions: Our findings suggest that constipation occurring as early as 20 or more years before the onset of motor symptoms is associated with an increased risk of Parkinson disease.

We investigated the association of Bell's palsy (BP) with the subsequent risk of Parkinson's disease (PD) using a case-control study design. We matched 196 incident cases of PD in Olmsted County, MN, to 196 general population controls with same age (+/-1 year) and sex, and we reviewed the complete medical records of cases and controls in a medical records-linkage system to detect BP. Six of the 196 patients with PD and none of the 196 controls were diagnosed with BP before PD (exact binomial probability, P = 0.02). The median age at occurrence of BP was 49.5 years (range, 15-84 years) and the median time between BP and the onset of PD was 27.5 years (range, 2-54 years). The findings were similar using a standardized incidence ratio (SIR) approach, but were not statistically significant. This initial association between BP and PD awaits replication.

We describe the presenting features and long-term outcomes of patients with electrophysiologically-confirmed psychogenic tremor. Clinical information for all patients with psychogenic tremor confirmed by our Movement Disorders Neurophysiology Laboratory (2003-2004) was reviewed. A follow-up questionnaire was administered to all included patients in 2007. Psychogenic tremor was documented in 62 patients; 33 responded to the questionnaire (53%). Median onset-age was 50 years (range, 15-71); 23 were female (70%). Clinical certainty of psychogenic etiology was: definite, 8 (24%); probable, 16 (49%), and possible, 9 (27%). Characteristic electrodiagnostic features of psychogenic tremor were documented in all. All but two patients were ultimately given a definite diagnosis of psychogenic tremor; recommended psychiatric consultation was only done by 12 (36%). Twenty-one patients (64%) rated tremor disability as moderate or severe after a median follow-up of 5.1 years (range, 3.3-19). Improvement occurred spontaneously in 5 (15%), and after a specific intervention in 4 (12%), whereas 3 (9%) had mild but unchanged symptoms. The mean duration of symptoms, prior to diagnosis with psychogenic tremor, was significantly shorter for patients with mild or no tremor at follow-up (P = 0.037). Physiologically-confirmed psychogenic tremor carries a poor prognosis, with unremitting or worse tremor persisting 3-years after diagnosis in most.

There is increasing laboratory evidence that estrogen has neuroprotective effects that may include improved synapse formation, increased cerebral blood flow and glucose metabolism, antioxidant activity, and reduced deposition of β-amyloid in the brain. Clinical and epidemiological evidence, however, has lagged behind. It could well be that there is a critical age window within which neuroprotective effects express themselves. This study examined the association between oophorectomy, performed before the start of menopause for reasons unrelated to tumor, with the risk of subsequent cognitive impairment or dementia as disclosed by a modified form of the Telephone Interview for Cognitive Status. The final study groups included 813 women having unilateral oophorectomy; 676 having bilateral oophorectomy; and 1472 referent women matched for age with the surgical groups. Compared to referent women, those undergoing unilateral or bilateral oophorectomy had an increased risk of cognitive impairment or dementia. The hazard ratio was 1.46 and the 95% confidence interval 1.13-1.90 after adjusting for education and a history of depression. The risk of cognitive dysfunction or dementia increased as the age at the time of oophorectomy declined, and was significantly increased when oophorectomy was done before age 49 years. The findings were independent of the indication for oophorectomy, and were similar following unilateral and bilateral oophorectomy. Oophorectomy-either unilateral or bilateral-appears to carry with it an increased risk of cognitive impairment or dementia when performed before the start of menopause. This study is one of the first to support the idea of a critical age window for protective effects of estrogen on the brain. The findings encourage a reassessment of prophylactic oophorectomy in premenopausal women and also of estrogen therapy following oophorectomy.

Objective: To determine if future studies of coenzyme Q10 and GPI-1485 in Parkinson disease (PD) may be warranted. Methods: We conducted a randomized, double-blind, calibrated futility clinical trial of coenzyme Q10 and GPI-1485 in early untreated PD using placebo data from the DATATOP study to establish the futility threshold. Results: The primary outcome measure (change in total Unified Parkinson's Disease Rating Scale scores over 1 year) did not meet the prespecified criteria for futility for either agent. Secondary analyses using calibration controls and other more recent placebo data question the appropriateness of the predetermined definition of futility, and suggest that a more restrictive threshold may be needed. Conclusions: Coenzyme Q10 and GPI-1485 may warrant further study in Parkinson disease, although the data are inconsistent. Additional factors (cost, availability of other agents, more recent data on placebo outcomes, other ongoing trials) should also be considered in the selection of agents for Phase III studies. NEUROLOGY 2007;68:20-28

Atypical parkinsonism (AP) has a considerable impact on the lives not only of patients but also of their carers. The aim of this study was to develop an instrument for assessing the quality of life (QoL) of carers of patients with AP. A 40-item pool was generated from in-depth interviews with carers of patients with AP, a thorough review of the existing literature and consultation with movement disorder experts. Item refinement and reduction was performed using the results of pilot testing and a survey in 282 carers of multiple system atrophy (MSA) patients and 226 carers of progressive supranuclear palsy (PSP) patients. A validation study, with responses of 243 carers of MSA and 187 carers of PSP patients, was undertaken to evaluate the psychometric properties of the final 26-item scale. The validation study results suggest that the scale is unidimensional and has high internal consistency (Cronbach’s α = 0.96). The correlations of scale scores with patients’ health status and QoL measures, such as PDQ-39 summary score and EQ-5D index (Spearman’s ρ = 0.56 and −0.31, respectively, P

Multiple system atrophy is characterized by autonomic failure along with motor symptoms of parkinsonism and/or cerebellar ataxia. There are differing reports on the influence of certain clinical features, including motor subtype (multiple system atrophy-parkinsonism versus multiple system atrophy-cerebellar ataxia), age of onset, gender, and early autonomic symptoms, on the survival in patients with multiple system atrophy. We sought to evaluate overall survival and predictors of survival in a large cohort of patients with multiple system atrophy seen at a single referral centre where objective autonomic testing is routinely performed for this indication. All cases of multiple system atrophy evaluated at Mayo Clinic, Rochester and assessed with an autonomic reflex screen between January 1998 and December 2012 were retrospectively reviewed. A total of 685 patients were identified; 594 met criteria for probable multiple system atrophy, and 91 for possible multiple system atrophy. Multiple system atrophy-parkinsonism was the predominant subtype in 430 patients (63%). Average age of onset was earlier in multiple system atrophy-cerebellar ataxia (58.4 years) compared to multiple system atrophy-parkinsonism (62.3 years; P < 0.001). Median disease duration from symptom onset to death was 7.51 years (95% confidence interval 7.18-7.78) while time from diagnosis to death was 3.33 years (95% confidence interval 2.92-3.59). There was no difference in survival between motor subtypes of multiple system atrophy (P = 0.232). An initial motor symptom was most common (61%) followed by autonomic onset (28%) and combined motor and autonomic symptoms (11%). The initial onset of either motor or autonomic symptoms did not influence length of survival. However, a number of clinical and autonomic laboratory features predicted unfavourable survival in a univariate analysis. A multivariate model retained the following unfavourable predictors of survival: (i) falls within 3 years of onset (hazard ratio 2.31, P < 0.0001); (ii) bladder symptoms (hazard ratio 1.96, P < 0.0001); (iii) urinary catheterization within 3 years of symptom onset (hazard ratio 1.67, P < 0.003); (iv) orthostatic intolerance within 1 year of symptom onset (hazard ratio 1.28, P < 0.014); (v) older age of onset (hazard ratio 1.02, P = 0.001); and (vi) degree of autonomic failure as measured by a validated composite autonomic severity score (hazard ratio 1.07, P < 0.0023). We conclude that carefully selected clinical features can be used to predict survival in patients with multiple system atrophy. Autonomic testing adds an additional, independent predictor of survival, demonstrating its value not only in the diagnosis of multiple system atrophy but also as prognostic marker.

Objective: To evaluate the clinical, electrophysiologic, and treatment outcome features of orthostatic tremor (OT) in a large case series. Methods: We performed medical record review of 184 patients who met clinical and electrodiagnostic criteria for OT from 1976 to 2013 at the Mayo Clinic. Demographic, clinical, electrophysiologic, and treatment data were extracted. Results: The majority of OT cases were female (63.6%) and mean age at onset was 59.3 years (range 13–85 years). Diagnosis was delayed by a mean of 7.2 years (range 0–44 years). The average tremor frequency was 15.7 Hz (range 12.5–20 Hz), and transmitted to the arms on weight-bearing (95.5%). Patients reported a spectrum of progressive orthostatic leg symptoms, relieved by sitting or leaning. Falls were reported in 24.1%. Coexistent neurologic disorders included essential tremor (22.8%), other tremor (4.9%), and parkinsonism (8.7%). Family history of OT was noted in 4.9%. Of 46 medications trialed, 24 failed to provide any benefit. Benzodiazepines provided at least mild benefit in 55.9%, and moderate to marked benefit in 31.5%; β-blockers (31.0%) and anticonvulsants (25.0%) provided mild benefit, and the remainder were largely ineffective. Medication benefit waned over time. Deep brain stimulation (DBS) was effective in 2 cases. Conclusion: OT predominantly affects female seniors, and the diagnosis should be considered with any orthostatic-induced leg symptoms, and confirmed by surface EMG. Benzodiazepines are the most efficacious treatment, followed by β-blockers and anticonvulsants. DBS should be further explored for treatment.

Objective: To develop a new patient-reported outcome measure for progressive supranuclear palsy (PSP) and to test its psychometric properties. Methods: First, the authors generated a pool of potential scale items from in-depth patient interviews. Second, the authors administered these items, in the form of a questionnaire, to a sample of people with PSP and traditional psychometric methods were used to develop a rating scale satisfying standard criteria for reliability and validity. Third, the authors examined the psychometric properties of the rating scale in a second sample. Results: In stage 1, a pool of 87 items was generated from 27 patient interviews. In stage 2, a scale with two subscales (physical, 22 items; mental, 23 items), satisfying standard criteria for reliability and validity, was developed from the response data of 225 patients with PSP. In stage 3, the scale was examined in 188 people with PSP. Missing data were low, scores in both subscales were evenly distributed, floor and ceiling effects were small. Reliability was high (Cronbach’s alpha 0.93, 0.95; test-retest 0.95, 0.92). Validity was supported by the interscale intercorrelation (0.60), factor analysis, and the magnitude and pattern of correlations with four other rating scales, disease severity, and disease duration. The psychometric properties of the new scale were similar in the United Kingdom and North America, and in clinic- and community-based samples studied. Conclusions: The Progressive Supranuclear Palsy Quality of Life scale (PSP-QoL) may be a helpful patient-reported scale for clinical trials and studies in PSP.

In an inception cohort of 196 Olmsted County, Minnesota, residents with Parkinson's disease (PD) first recognized in 1976 to 1995, we tested whether the increased risk of bone fractures is associated with concomitant dementia. Using the data resources of the Rochester Epidemiology Project, information about PD, dementia, other clinical risk factors for fracture and fracture events was obtained from review of complete inpatient and outpatient medical records spanning each subject's residence in the community. Compared to an equal number of age- and sex-matched non-PD referent subjects from the community, PD patients were at a 2.2-fold increased risk of fractures generally and a 3.2-fold greater risk of hip fractures specifically. Adjusting for age, the independent predictors of overall fracture risk in the PD subjects included female sex (hazard ratio [HR] 1.6; 95% confidence interval [CI], 1.1-2.3), dementia (HR, 1.6; 95% CI, 1.1-2.4) and chronic depression, which was associated with a reduced risk (HR, 0.4; 95% CI, 0.2-0.8). Hip fractures were predicted by dementia (HR, 2.2; 95% CI, 1.2-4.1). The increased fracture risk in patients with PD is not entirely explained by concomitant dementia, and additional study is needed to determine the relative contributions to fracture risk of falls versus bone loss in these patients.

The burden of comorbidity in Parkinson's disease (PD) remains unclear. All Olmsted County, Minnesota, residents with incident PD in 1976-1995 (n = 197) plus one age- and sex-matched non-PD referent subject per case were followed for all clinical diagnoses from 5 years before through 15 years after index (i.e., year of PD onset for each case and same year for the referent subject). Both members of a case-referent pair were censored at death or emigration of either member to ensure equivalent follow-up. Cases and referent subjects were compared for summary comorbidity (Charlson index) and for the likelihood of having one or more diagnoses within each International Classification of Diseases chapter/subchapter. Before index, the groups were similar for all comparisons. After index, cases had a higher likelihood of diagnoses within the chapters "Mental Disorders" and "Diseases of the Genitourinary System," and within the subchapters "Organic Psychotic Conditions," "Other Psychoses," "Neurotic/Personality/Other Nonpsychotic Disorders," "Hereditary/Degenerative Diseases of Central Nervous System," "Symptoms," "Other Diseases of Digestive System," "Other Diseases of Urinary System," "Diseases of Veins/Lymphatics/Other Circulatory System Diseases," "Fractures of Lower Limb," "Other Diseases of Skin/Subcutaneous Tissue," "Osteopathies/Chrondropathies/Acquired Musculoskeletal Deformities," and "Pneumonia and Influenza." The excess morbidity and mortality observed for persons with PD are consistent with recognized PD sequelae.

To avoid the possible confounding effect of population stratification, we employed a discordant sibling study design and a liberalization of the sibling transmission disequilibrium test to confirm the association of the S18Y variant of the ubiquitin carboxi-terminal hydrolase L1 (UCHL1) gene with Parkinson's disease (PD). The study included 497 case-control pairs (427 case-unaffected sibling pairs and 70 case-unrelated control pairs). Analyses confirmed a significant inverse association of the UCHL1 S18Y polymorphism with PD overall (OR=0.18, 95% CI=0.05-0.64, p=0.002, recessive model) and in several strata.

We investigated the risk of cancer after the diagnosis of Parkinson's disease (PD) through a historical cohort study. We used the medical records-linkage system of the Rochester Epidemiology Project to identify all incident cases of PD in Olmsted County, Minnesota from 1976 through 1995. Patients with PD were matched by age (+/- 1 year) and gender to referent subjects from the same population. For 196 patients and 185 referent subjects, we ascertained the incidence of cancer through medical records abstraction between the date of diagnosis (or index date) and death, loss to follow-up, or end of study. The risk of cancer was higher among patients than in referent subjects (relative risk [RR] = 1.64; 95% confidence interval [CI] = 1.15-2.35; P = 0.007). The RR did not change noticeably after adjustment for smoking. The increased risk was significant for nonmelanoma skin cancer (RR = 1.76; 95% CI = 1.07-2.89; P = 0.03), but not for other more severe types of cancer; therefore, we cannot exclude the occurrence of a surveillance bias. Among PD patients, there was no relation between the risk of cancer and the cumulative dose of levodopa received or the use of other PD medications.

There is little information on the frequency of movement disorders seen by physicians in the continent of Africa. We performed a medical record review of all patients seen in a university-based neurology clinic in Addis Ababa, Ethiopia, over 1 year to determine the frequency of movement disorders seen, disease characteristics, diagnostic evaluations, and treatment. A total of 15.1% of the neurological patients were seen for movement disorders. Of these, most were for parkinsonism (47.7%), followed by ataxia (16.5%), dystonia (8.3%), essential tremor (8.3%), chorea (7.3%), and miscellaneous (11.9%). Diagnostic evaluations were limited, but treatment was available, although expensive. In spite of the limitations, patients with movement disorders require and seek care in Ethiopia in proportions comparable to developed nations. This finding underlines the need for adequate training in movement disorders for physicians and neurologists in Africa.

The idea of a Global Health Section within the American Academy of Neurology (AAN) came from a group of neurologists with active work in sub-Saharan Africa, who believed that the AAN could provide a greater leadership role in supporting the advancement of quality neurologic training, research, and patient care in low and middle-income countries (LMICs). Initially a Special Interest Group, the Global Health Section was approved for full section status in September 2011 and endorsed by the AAN Board of Directors in October 2011. The Global Health Section currently consists of over 200 members. In a 2-part series, we present a summary of the Global Health Section strategic plan and vision for future activities.

An association study of four common polymorphisms in the DJ1 gene and Parkinson disease (PD) was conducted. PD probands were compared with their unaffected siblings matched by gender and closest age at study (416 vs 416) and with unrelated control subjects (691 vs 190). None of the four haplotype tagging single-nucleotide polymorphisms (SNPs) was associated with PD overall, but SNP1 (position 4,345 bp) and SNP3 (position 16,491 bp) were associated with PD in women (p = 0.03 and p = 0.002).

We report on an evaluation of coding variants within the parkin gene to assess their frequency in a North American clinical series of 313 Parkinson's disease (PD) cases and 192 unrelated controls. We hypothesized that the carrier frequency of parkin coding mutations, exon deletions, or duplications may be greater in PD cases. However, point mutations and exonic deletions/duplications, reported previously as pathogenic in homozygous or compound heterozygous individuals, occurred in both cases and controls with similar frequencies (3.8% in cases, 3.1% in controls). Furthermore, only stratified subanalyses detected any genetic association between the V380L common coding polymorphism and PD. We discuss the implication of parkin mutations for Parkinson's disease from this population perspective.

Objective: To study the validity of information provided by case and control subjects (or their proxies) about PD among their first-degree relatives. Methods: Secondary cases of PD were assessed both through a single informant (family history method) and through the study of each relative (family study method). The family study method was considered as the standard for comparison, and the sensitivity and specificity of the family history method were studied. Results: A total of 133 population-based case subjects and their 655 relatives were recruited, and 119 population-based control subjects and their 511 relatives. Sensitivity was 68% (95% CI = 47 to 85) for cases and 45% (95% CI = 17 to 77) for controls. Specificity was 99% (95% CI = 98 to 99) for cases and 100% (95% CI = 99 to 100) for controls. The odds ratio (OR) for family history of PD was 4.34 (95% CI = 1.63 to 11.58, p = 0.003) using the family history method and 1.86 (95% CI = 0.78 to 4.44, p = 0.16) using the family study method. The former significant OR more than doubled the latter not significant OR (relative bias = 133%). Bias was more pronounced for proxy interviews and for women informants, and when the relatives were siblings, were living, and were examined or had medical record documentation. Conclusions: Case subjects with PD (or their proxies) are more aware of PD among their first-degree relatives than control subjects (or their proxies); however, they overreport PD in relatives who are not affected. This causes a substantial family information bias.

Objective Botulinum toxin (BTX) injections have been used extensively in medicine; however, little is known about the factors predicting the loss of effectiveness of botulin toxin. Methods Using a clinical database, we identified 401 subjects who had been treated for movement disorders from 1998 through 2010 with onabotulinumtoxin A (BTX A) or who switched from BTX A to rimabotulinumtoxin B (BTX B). We compared patients who switched from type A to type B with patients using type A only with regard to number of visits, total number of injections, number of initial and final sites, number of initial units used, and duration of treatments. Results We observed that patients who switched from BTX A to B had a significantly higher number of initial injection sites than patients with BTX A only (BTX A to B median = 8.5; BTX A median = 6; p for difference = 0.006), had a higher number of final sites (BTX A to B median = 9 BTX A median = 7; p = 0.01), and were also more likely to have multiple reasons for injection (BTX A to B = 25.0%; botulin toxin A = 5.3%; p = 0.01). We did not find significant differences between groups based on the other variables. Conclusions Our findings suggest that higher number of sites rather than higher number of units or years of treatment are associated with the loss of effectiveness to BTX A. It is possible that the loss of effectiveness to the BTX is more strongly elicited when the injections are widely diffuse.

We correlated the clinical features with pathological findings in an autopsy series of cases of incident parkinsonism. We used the medical records-linkage system of the Rochester Epidemiology Project to identify all incident cases of parkinsonism in Olmsted County, MN, for the years 1976 to 1990. Medical histories were abstracted in a standardized manner. Included in this study were those incident cases who died and underwent autopsy. Brain sections were studied with routine histology and special stainings. A neuropathologist blinded to any clinical information assigned cases to neuropathological categories. We found 364 incident cases of parkinsonism of which 235 were deceased at the time of this study; there were 39 autopsied brains available for analysis (17% of deceased cases). Of the 16 patients diagnosed pathologically with Lewy body disease, documentation indicated that 8 had an early dementia, 3 had prominent dysautonomia, and 2 had prominent ataxia. Of the 7 patients diagnosed pathologically with progressive supranuclear palsy, 4 had no documentation of supranuclear gaze palsy, and 3 had no documentation of early falls. Of the 3 patients diagnosed pathologically with multiple system atrophy, none had prominent ataxia or dysautonomia documented. Of the 5 patients with vascular disease at pathology, none had been given the clinical diagnosis of vascular parkinsonism. Of the 8 cases given the clinical diagnosis of drug-induced parkinsonism, 6 were found to have basal ganglia pathology. The autopsied cases in this study were not representative of all patients with parkinsonism, because atypical cases are more likely to come to autopsy than typical ones. Despite this selection bias, the retrospective data collection, and the small sample size, we made several observations that illustrate the difficulty in achieving an accurate antemortem diagnosis of parkinsonism.

We applied the incidence rates of parkinsonism and Parkinson's disease (PD) from Olmsted County, MN (1976–1990) to a hypothetical cohort undergoing the mortality rates observed in Minnesota, and computed the lifetime risk and the remaining lifetime risk of developing parkinsonism and PD. These risks were compared to cumulative incidences that do not take competing risks of death into account. The lifetime risk of developing parkinsonism from birth was 4.4% for men and 3.7% for women (ratio = 1.2). The corresponding risk of developing PD was 2.0% for men and 1.3% for women (ratio = 1.5). Because of the opposite effect of higher incidence and higher mortality rates in men, the lifetime risks were only slightly higher in men than in women. Lifetime cumulative incidences were consistently higher than lifetime risks; this difference was more pronounced in men and in older subjects. Lifetime risk estimates are useful in clinical practice, epidemiologic research, and public health.

Importance To our knowledge, a comprehensive study of the survival and causes of death of persons with synucleinopathies compared with the general population has not been conducted. Understanding the long-term outcomes of these conditions may inform patients and caregivers of the expected disease duration and may help with care planning. Objective To compare survival rates and causes of death among patients with incident, clinically diagnosed synucleinopathies and age- and sex-matched referent participants. Design, Setting, and Participants This population-based study used the Rochester Epidemiology Project medical records–linkage system to identify all residents in Olmsted County, Minnesota, who received a diagnostic code of parkinsonism from 1991 through 2010. A movement-disorders specialist reviewed the medical records of each individual to confirm the presence of parkinsonism and determine the type of synucleinopathy. For each confirmed patient, an age- and sex-matched Olmsted County resident without parkinsonism was also identified. Main Outcomes and Measures We determined the age- and sex-adjusted risk of death for each type of synucleinopathy, the median time from diagnosis to death, and the causes of death. Results Of the 461 patients with synucleinopathies, 279 (60.5%) were men, and of the 452 referent participants, 272 (60.2%) were men. From 1991 through 2010, 461 individuals received a diagnosis of a synucleinopathy (309 [67%] of Parkinson disease, 81 [17.6%] of dementia with Lewy bodies, 55 [11.9%] of Parkinson disease dementia, and 16 [3.5%] of multiple system atrophy with parkinsonism). During follow-up, 68.6% (n = 316) of the patients with synucleinopathies and 48.7% (n = 220) of the referent participants died. Patients with any synucleinopathy died a median of 2 years earlier than referent participants. Patients with multiple system atrophy with parkinsonism (hazard ratio, 10.51; 95% CI, 2.92-37.82) had the highest risk of death compared with referent participants, followed by those with dementia with Lewy bodies (hazard ratio, 3.94; 95% CI, 2.61-5.94), Parkinson disease with dementia (hazard ratio, 3.86; 95% CI, 2.36-6.30), and Parkinson disease (hazard ratio, 1.75; 95% CI, 1.39-2.21). Neurodegenerative disease was the most frequent cause of death listed on the death certificate for patients, and cardiovascular disease was the most frequent cause of death among referent participants. Conclusions and Relevance Individuals with multiple system atrophy with parkinsonism, dementia with Lewy bodies, and Parkinson disease dementia have increased mortality compared with the general population. The mortality among persons with Parkinson disease is only moderately increased compared with the general population.

Neurological and autonomic presentation in multiple system atrophy (MSA) may predict early mortality. Quantification of early autonomic failure as a mortality predictor is lacking. Early neurological and autonomic clinical features were retrospectively reviewed in 49 MSA cases (median age at onset, 56.1 years; 16 women) confirmed by autopsy at Mayo Clinic. When available, the 10-point composite autonomic severity score derived from the autonomic reflex screen provided quantification of the degree of autonomic failure and thermoregulatory sweat test quantitated body surface anhidrosis. Symptoms at onset were autonomic in 50%, parkinsonian in 30%, and cerebellar in 20% of cases. Survival (median [95% confidence interval]) was 8.6 [6.7-10.2] years. Survival was shorter in patients with early laboratory evidence of generalized (composite autonomic severity score ≥ 6) autonomic failure (7.0 [3.9-9.8] vs. 9.8 [4.6-13.8] years; P = 0.036), and early requirement of bladder catheterization (7.3 [3.1-10.2] vs. 13.7 [8.5-14.9] years; P = 0.003) compared with those without these clinical features. On Cox proportional analysis, prognostic indicators of shorter survival were older age at onset (hazard ratio [95% confidence interval], 1.04 [1.01-1.08]; P = 0.03), early requirement of bladder catheterization (7.9 [1.88-38.63]; P = 0.004), and early generalized (composite autonomic severity score ≥ 6) autonomic failure (2.8 [1.01-9.26]; P = 0.047). Gender, phenotype, and early development of gait instability, aid-requiring ambulation, orthostatic symptoms, neurogenic bladder, or significant anhidrosis (thermoregulatory sweat test ≥ 40%) were not indicators of shorter survival. Our data suggest that early development of severe generalized autonomic failure more than triples the risk of shorter survival in patients with MSA.

We studied the association of Parkinson's disease (PD) with type of menopause (natural or surgical), age at menopause, and postmenopausal estrogen replacement therapy using a case-control design. We used the medical records-linkage system of the Rochester Epidemiology Project to identify 72 women who developed PD in Olmsted County, MN, during the twenty years 1976-1995. Each incident case was matched by age (+/- 1 year) to a general population control subject. We collected exposure data through review of the complete medical records of cases and control subjects in the system. PD cases had undergone hysterectomy (with or without unilateral oophorectomy) significantly more often than control subjects (odds ratio [OR] = 3.36; 95% confidence interval [CI] = 1.05-10.77). In addition, PD cases had experienced early menopause (< or = 46 years) more commonly than control subjects (OR = 2.18; 95% CI = 0.88-5.39). Finally, PD cases had used estrogens orally or parenterally for at least 6 months after menopause less frequently (8%) than control subjects (14%; OR = 0.47; 95% CI = 0.12-1.85). However, the findings for early menopause and estrogen replacement therapy were not statistically significant. Despite the limited sample size of this exploratory study, we hypothesize that there is an increased risk of PD in conditions causing an early reduction in endogenous estrogen. This hypothesis needs to be confirmed in a larger study.

Objective: To investigate time trends in the incidence of parkinsonism and PD over a 15-year period (1976 to 1990).Methods: The authors used the medical records–linkage system of the Rochester Epidemiology Project to identify incidence cases of parkinsonism in Olmsted County, MN, over three 5-year periods, 1976 to 1980, 1981 to 1985, and 1986 to 1990. PD and other types of parkinsonism were classified using defined criteria. Population denominators were derived from census data and were corrected by removing prevalent cases of parkinsonism.Results: Over the 15 years of the study, 364 cases of parkinsonism were identified; 154 (42%) of them had PD. The incidence of parkinsonism remained stable over the three 5-year periods for the age classes 0 to 39, 40 to 59, and 60 to 69 years. For the age class 70 to 99 years, there was some increase over time mainly owing to an increased incidence of drug-induced parkinsonism. The incidence of PD remained stable over the three 5-year periods for all age classes. Results were similar when considering men and women separately. No birth-cohort effect was present for parkinsonism. Comparison with three previous studies in the same population did not reveal any major long-term secular trends in the incidence of parkinsonism.Conclusions: The findings for PD over 15 years and comparison of the findings with historical data for parkinsonism over half a century suggest that no major environmental risk factors for PD (e.g., environmental toxins, drugs, diet constituents, or infectious agents) were introduced or removed from this population during these periods.

Background Othello’s syndrome (OS) is a delusion of infidelity. We describe seven cases of OS in Parkinson’s disease (iPD) patients using dopamine agonists. Methods We searched the Mayo Clinic Medical Records System to identify all patients with OS. Clinical data abstracted include sex, age of onset of iPD, age of onset of OS, medications, effect of discontinuing the dopamine agonist, neuroimaging, and comorbidities. Results Seven non-demented iPD patients with dopamine agonist implementation time locked to the development and resolution of OS are reported. The average age of iPD onset was 46.6 years (Standard deviation: 5.0 years), and OS onset was 53.7 years (7.1 years). All seven patients had significant marital conflict as a result of the delusions. Conclusions: OS can be associated with dopamine agonist use and can lead to serious consequences. Dopamine agonist cessation eliminates the delusion of infidelity and should be the first treatment option.

To study the association of PD with preceding smoking, alcohol, and coffee consumption using a case-control design.The authors used the medical records linkage system of the Rochester Epidemiology Project to identify 196 subjects who developed PD in Olmsted County, MN, during the years 1976 to 1995. Each incident case was matched by age (+/-1 year) and sex to a general population control subject. The authors reviewed the complete medical records of cases and control subjects to abstract exposure information.For coffee consumption, the authors found an OR of 0.35 (95% CI = 0.16 to 0.78, p = 0.01), a dose-effect trend (p = 0.003), and a later age at PD onset in cases who drank coffee compared with those who never did (median 72 versus 64 years; p = 0.0002). The inverse association with coffee remained significant after adjustment for education, smoking, and alcohol drinking and was restricted to PD cases with onset at age72 years and to men. The OR for cigarette smoking was 0.69 (95% CI = 0.45 to 1.08, p = 0.1). The authors found no association between PD and alcohol consumption. Extreme or unusual behaviors such as tobacco chewing or snuff use and a diagnosis of alcoholism were significantly more common in control subjects than cases.These findings suggest an inverse association between coffee drinking and PD; however, this association does not imply that coffee has a direct protective effect against PD. Alternative explanations for the association should be considered.

We studied the association between preceding psychiatric disorders and Parkinson's disease (PD) using a case-control design. We used the medical records-linkage system of the Rochester Epidemiology Project to identify 196 subjects who developed PD in Olmsted County, Minnesota, during the years 1976-1995. Each case was matched by age (+/-1 yr) and sex to a general population control. We reviewed the complete medical records of cases and control subjects to detect preceding psychiatric disorders. The frequency of psychiatric disorders was higher in cases than in control subjects; the odds ratio was 2.2 for anxiety disorders (95% confidence interval [95% CI] = 1.4-3.4; p = 0.0003), 1.9 for depressive disorders (95% CI = 1.1-3.2; p = 0.02), and 2.4 for both anxiety disorders and depressive disorders occurring in the same individual (95% CI = 1.2-4.8; p = 0.02). When we restricted analyses to disorders present 5 years or more before the onset of motor symptoms of PD, the association with depressive disorders lost statistical significance. However, the association with anxiety disorders remained significant for disorders present 5, 10, or 20 years before onset of motor symptoms. Our results suggest that anxiety disorders and depressive disorders are associated with PD and that the causative process or the risk factors underlying PD are present many years before the appearance of motor symptoms.

Information on the incidence of progressive supranuclear palsy (PSP) is limited; incidence rates for multiple system atrophy (MSA) are not available. We studied the incidence of PSP and MSA in Olmsted County, Minnesota, for the years 1976 to 1990. This study was part of a larger investigation of all forms of parkinsonism. We used the medical records-linkage system of the Rochester Epidemiology Project to identify all subjects whose records contained documentation of any form of parkinsonism, related neurodegenerative diseases, or tremor of any type. A nurse abstractor screened the records and, when applicable, a neurologist reviewed them to determine the presence or absence of parkinsonism. Cases of parkinsonism were classified using specified diagnostic criteria. Population denominators were derived from census data and were corrected by removing prevalent cases of parkinsonism. Over the 15 years of the study, we found 16 incident cases of PSP and nine incident cases of MSA. No cases of PSP or MSA had onset before age 50 years. The average annual incidence rate (new cases per 100,000 person-years) for ages 50 to 99 years was 5.3 for PSP and 3.0 for MSA. The incidence of PSP increased steeply with age from 1.7 at 50 to 59 years to 14.7 at 80 to 99 years, and was consistently higher in men. Median survival time from symptom onset was 5.3 years for PSP and 8.5 years for MSA. The incidence of PSP increases with age and is consistently higher in men at all ages. PSP and MSA are more common than previously recognized.

In the first part of this series, we outlined the current state of global health in neurology. In this second part, we provide an analysis of the role the AAN Global Health Section can play and outline the Section's vision and goals.

Editors' Note: Drs. Benito-Leon and Domingo-Santos express their surprise at the lack of apparent cerebellar involvement in the “Orthostatic tremor: Clinical, electrophysiologic, and treatment findings in 184 patients” study. They also suggest that orthostatic tremor (OT) may be part of other neurologic disorders such as Parkinson disease (PD) or parkinsonism. Hassan et al., authors of the study, highlight the lack of evidence for cerebellar involvement and are hopeful for a better unifying pathophysiology to explain OT. Boyd et al. believe that there is an association between hepatitis C virus treatment and development of PD and ask the authors of “Hepatitis C virus infection as a risk factor for Parkinson disease: A nationwide cohort study” to …

Background Multiple system atrophy (MSA) is a sporadic progressive neurodegenerative disorder characterised by autonomic failure, manifested as orthostatic hypotension or urogenital dysfunction, with combinations of parkinsonism that is poorly responsive to levodopa, cerebellar ataxia and corticospinal dysfunction. Published autopsy confirmed cases have provided reasonable neurological characterisation but have lacked adequate autonomic function testing. Objectives To retrospectively evaluate if the autonomic characterisation of MSA is accurate in autopsy confirmed MSA and if consensus criteria are validated by autopsy confirmation. Methods 29 autopsy confirmed cases of MSA evaluated at the Mayo Clinic who had undergone formalised autonomic testing, including adrenergic, sudomotor and cardiovagal functions and Thermoregulatory Sweat Test (TST), from which the Composite Autonomic Severity Score (CASS) was derived, were included in the study. Results Patient characteristics: 17 men, 12 women; age of onset 57±8.1 years; disease duration to death 6.5±3.3 years; first symptom autonomic in 18, parkinsonism in seven and cerebellar in two. Clinical phenotype at first visit was MSA-P (predominant parkinsonism) in 18, MSA-C (predominant cerebellar involvement) in eight, pure autonomic failure in two and Parkinson9s disease in one. Clinical diagnosis at last visit was MSA for 28 cases. Autonomic failure was severe: CASS was 7.2±2.3 (maximum 10). TST% was 65.6±33.9% and exceeded 30% in 82% of patients. The most common pattern was global anhidrosis. Norepinephrine was normal supine (203.6±112.7) but orthostatic increment of 33.5±23.2% was reduced. Four clinical features (rapid progression, early postural instability, poor levodopa responsiveness and symmetric involvement) were common. Conclusion The pattern of severe and progressive generalised autonomic failure with severe adrenergic and sudomotor failure combined with the clinical phenotype is highly predictive of MSA.

© Cambridge University Press 2011. Introduction Progressive supranuclear palsy (PSP) is a neurodegenerative disorder causing parkinsonism, visual dysfunction, and balance impairment, as well as cognitive impairment and psychiatric complications. These problems, together with the emotional and social consequences of having a progressively disabling disease with shortened life expectancy, have an enormous impact on patients' health-related quality of life (HRQoL). PSP was first delineated as a distinct disorder, separate from Parkinson's disease, in 1962. It is sometimes referred to as Steele–Richardson–Olszewski syndrome after the scientists who originally described the condition. It is estimated that the disease has a prevalence of 6 per 100,000, similar to that of motor neuron disease, with the average age of onset being in the seventh decade. Mean survival from the onset of symptoms is approximately 6 years. To date, there has been little validation of any HR-QoL generic instruments in this patient group. In one small-scale study, some limited evidence for the appropriateness of the European Quality of Life Five Dimensions (EQ-5D) in this patient group was found, but less support was found for the 36-Item Short-Form Health Survey (SF-36), which some patients indicated did not cover areas of relevance to them. The Parkinson's Disease Questionnaire (PDQ-39) has been assessed for its suitability in this patient group, but it was found to lack some aspects of quality of life that are important to patients with PSP.

Objective: It has been suggested that people who develop Parkinson disease (PD) may have a characteristic premorbid personality. We tested this hypothesis using a large historical cohort study with long follow-up. Methods: We conducted a historical cohort study in the region including the 120-mile radius centered in Rochester, MN. We recruited 7,216 subjects who completed the Minnesota Multiphasic Personality Inventory (MMPI) for research at the Mayo Clinic from 1962 through 1965 and we considered 5 MMPI scales to measure sensation seeking, hypomania, positive emotionality, social introversion, and constraint. A total of 6,822 subjects (94.5% of the baseline sample) were followed over 4 decades either actively (via interview and examination) or passively (via medical records). Results: During follow-up, 227 subjects developed parkinsonism (156 developed PD). The 3 MMPI scales that we selected to measure the extroverted personality construct (sensation seeking, hypomania, and positive emotionality) did not show the expected pattern of higher scores associated with reduced risk of PD. Similarly, the 2 MMPI scales that we selected to measure the introverted personality construct (social introversion and constraint) did not show the expected pattern of higher scores associated with increased risk of PD. However, higher scores for constraint were associated with an increased risk of all types of parkinsonism pooled together (hazard ratio 1.39; 95% CI 1.06–1.84; p = 0.02). Conclusions: We suggest that personality traits related to introversion and extroversion do not predict the risk of PD.

The objective of this study was to compare subjective health status and its correlates in progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). One hundred eighty-eight patients with PSP and 286 patients with MSA completed EQ-5D and Hospital Depression and Anxiety Scale. The impact on mobility, usual activities, and self-care was similarly high in both groups after similar duration. Fifty-six percent of PSP and 43% of MSA had probable depression, and 37% of both groups had probable anxiety. Patients with PSP had significantly higher depression scores, but groups did not differ in anxiety scores. Patients with MSA had significantly greater pain/discomfort than patients with PSP. The most important association with subjective health status was with depressive symptoms, which accounted for 38% and 29% of EQ-5D variance in patients with PSP and MSA, followed by disease severity and anxiety scores. We conclude that depressive symptoms were common in both disorders, but more severe in PSP. Anxiety symptoms affected 37% of patients in both groups and contributed to impaired subjective health status. Pain was more problematic in MSA than PSP.

It has been suggested that anemia may be a risk factor for dementia, for restless legs syndrome, and for Parkinson disease (PD). Thus, we investigated the association of anemia with the subsequent risk of PD using a case-control study design.We used the medical records-linkage system of the Rochester Epidemiology Project to identify 196 subjects who developed PD in Olmsted County, Minnesota, from 1976 through 1995. Each incident case was matched by age (+/-1 year) and sex to a general population control. We reviewed the complete medical records of cases and controls in the system to detect anemia defined using the World Health Organization criteria.Anemia was more common in the history of cases than of controls (odds ratio 2.00, 95% confidence interval 1.31-3.06, p = 0.001). The association remained significant after adjustment for cigarette smoking, exposure to pesticides, or hysterectomy (in women). The association was not significantly different between men and women, or between PD patients with or without rest tremor. Analyses stratified by time of onset of anemia showed a greater association for anemia that started 20 to 29 years before the onset of PD. Hemoglobin levels were slightly but consistently lower in cases than in controls across all ages.Our results support an association between anemia experienced early in life and the later development of Parkinson disease. The interpretation of this association remains uncertain.

Objective To describe and provide audiovisual documentation of a syndrome of polymyoclonus, laryngospasm, and cerebellar ataxia associated with adenocarcinoma and multiple neural cation channel autoantibodies. Design Case report withvideo. Setting University hospitals. Patient A 69-year-old woman presented with subacute onset of whole-body tremulousness and laryngospasm attributed to gastroesophageal reflux. Results Further evaluation revealed polymyoclonus, cerebellar ataxia, and laryngospasm suspicious of an underlying malignant neoplasm. Surface electromyography of multiple limb muscles confirmed the presence of polymyoclonus. The patient was seropositive for P/Q-type voltage-gated calcium channel antibody; subsequently, whole-body fluorine 18 fluorodeoxyglucose positron emission tomography and cervical lymph node biopsy revealed widespread metastatic adenocarcinoma. Follow-up serologic evaluation revealed calcium channel antibodies (P/Q type and N type) and potassium channel antibody. Conclusions We highlight the importance of recognizing polymyoclonus. To our knowledge, this is also the first description of a syndrome of polymyoclonus, laryngospasm, and ataxia associated with adenocarcinoma and these cation channel antibodies.

We investigated the association of Bell's palsy (BP) with the subsequent risk of Parkinson's disease (PD) using a case-control study design. We matched 196 incident cases of PD in Olmsted County, MN, to 196 general population controls with same age (+/-1 year) and sex, and we reviewed the complete medical records of cases and controls in a medical records-linkage system to detect BP. Six of the 196 patients with PD and none of the 196 controls were diagnosed with BP before PD (exact binomial probability, P = 0.02). The median age at occurrence of BP was 49.5 years (range, 15-84 years) and the median time between BP and the onset of PD was 27.5 years (range, 2-54 years). The findings were similar using a standardized incidence ratio (SIR) approach, but were not statistically significant. This initial association between BP and PD awaits replication.

OBJECTIVE To determine the frequency of new-onset compulsive gambling or hypersexuality among regional patients with Parkinson disease (PD), ascertaining the relationship of these behaviors to PD drug use. PATIENTS AND METHODS We retrospectively reviewed the medical records of patients from 7 rural southeastern Minnesota counties who had at least 1 neurology appointment for PD between July 1, 2004, and June 30, 2006. The main outcome measure was compulsive gambling or hypersexuality developing after parkinsonism onset, including the temporal relationship to PD drug use. RESULTS Of 267 patients with PD who met the study inclusion criteria, new-onset gambling or hypersexuality was documented in 7 (2.6%). All were among the 66 patients (10.6%) taking a dopamine agonist. Moreover, all 7 (18.4%) were among 38 patients taking therapeutic doses (defined as ≥2 mg of pramipexole or 6 mg of ropinirole daily). Behaviors were clearly pathologic and disabling in 5: 7.6% of all patients taking an agonist and 13.2% of those taking therapeutic doses. Of the 5 patients, 2 had extensive treatment for what was considered a primary psychiatric problem before the agonist connection was recognized. CONCLUSION Among the study patients with PD, new-onset compulsive gambling or hypersexuality was documented in 7 (18.4%) of 38 patients taking therapeutic doses of dopamine agonists but was not found among untreated patients, those taking subtherapeutic agonist doses, or those taking carbidopa/levodopa alone. Behaviors abated with discontinuation of agonist therapy or dose reduction. Because this is a retrospective study, cases may have been missed, and hence this study may reflect an underestimation of the true frequency. Physicians who care for patients taking these drugs should recognize the drug's potential to induce pathologic syndromes that sometimes masquerade as primary psychiatric disease.

Objective: To study the association between several personality traits and all-cause mortality. Methods: We established a historical cohort of 7216 subjects who completed the Minnesota Multiphasic Personality Inventory (MMPI) for research at the Mayo Clinic from 1962 to 1965, and who resided within a 120-mile radius centered in Rochester, MN. A total of 7080 subjects (98.1%) were followed over four decades either actively (via a direct or proxy telephone interview) or passively (via review of medical records or by obtaining their death certificates). We examined the association of pessimistic, anxious, and depressive personality traits (as measured using MMPI scales) with all-cause mortality. Results: A total of 4634 subjects (65.5%) died during follow-up. Pessimistic, anxious, and depressive personality traits were associated with increased all-cause mortality in both men and women. In addition, we observed a linear trend of increasing risk from the first to the fourth quartile for all three scales. Results were similar in additional analyses considering the personality scores as continuous variables, in analyses combining the three personality traits into a composite neuroticism score, and in several sets of sensitivity analyses. These associations remained significant even when personality was measured early in life (ages 20–39 years). Conclusions: Our findings suggest that personality traits related to neuroticism are associated with an increased risk of all-cause mortality even when they are measured early in life.